ABSTRACT. The aim of this article is to broaden the epistemological basis for investigating the current shift to cognitive-cultural economies and the resurgence of cities and its socio-spatial articulation. The point of departure here is that the drivers of the structural changes are indeed more or less ubiquitous, but are played out in different national institutional and urban contexts resulting in potentially diverging cognitive-cultural economies. Four main drivers of change after 1980 are distinguished. The first is the rise of a new technological paradigm based on digital technology. The second is the thrust towards deregulation and privatization as planks of the neo-liberal political programme. The third is the intensification of all kinds of linkages between regions across the globe. The fourth driver constitutes the processes of individualization and increasing reflexivity that have fragmented consumer markets. By identifying distinct filters which might shape and mould the impact of these more general drivers on concrete urban areas, a comprehensive framework is presented that can be used to analyse and compare the trajectories of cities while linking them to a larger narrative of societal change. A central line of reasoning is that agglomeration economies – pivotal in Allen Scott's analysis of the emergence of a cognitive-cultural economy – are themselves embedded in concrete social and institutional contexts which impact on how they are played out. To make this point, we build upon Richard Whitley's business systems. Given this institutional diversity, we expect that various institutional contexts will generate different cognitive-cultural economies.